Aqueous Solubility−Molecular Size Relationships:  A Mechanistic Case Study Using C₁₀- to C₁₉-Alkanes

Abstract

Saturated hydrocarbons are important constituents of petroleum products. Their behavior in water, the most prevalent environmental solvent, is of relevance with regard to environmental partitioning. Due to their negligible attractive interactions with water, they are suitable compounds for a mechanism-based validation of the relationship between molecular size and the solubility in water. To that end, we measured the aqueous solubility of aliphatic and alicyclic hydrocarbons with 10 to 19 carbon atoms employing the slow-stirring experiment. Moreover, we compiled data on molecular weight and molar volume at the boiling point as macroscopic size parameters and calculated quantum-chemical molecular size parameters. The aqueous solubility data span a range from 6 × 10 -6 M to 4 × 10 -11 M with coefficients of variation of less than 15% except for 2,6,10,14-tetramethylpentadecane (39%). The relationships of the experimentally determined solubility values with the macroscopic reflected the general trend of decreasing solubility with increasing molecular size, but discriminated between n-and branched alkanes. This indicates that these parameters do not reflect the solute-solvent interactions at the microscopic level. Interpretation of the experimentally observed solubility data based on theoretical considerations of the conformation and the constitution of alkanes is consistent with the following overall picture: For a given n-alkane in aqueous solution, the all-trans conformation is preferred over folded geometries. Within alkanes, molecular size is the primary determinant of their solubility in water, and increasing molecular size results in a decrease in water solubility mainly due to the increased free energy penalty for cavity formation in water. The solvent-accessible molecular volume and surface area appeared to be valid reflections of the molecular size.

Modeling Ostwald ripening rate of styrene miniemulsions stabilized by a homolog of n-alkane costabilizers

“…5. By contrast, the C Ý,2 -vs.-carbon number of C n H 2n+2 profile attained from this work seems different from those reported in the literature [22][23][24]. In addition, the C Ý,2 -vs.-carbon number of C n H 2n+2 data presented in this study deviate significantly from results predicted by group contribution model [25] and molecular dynamics simulations [26].…”

“…Nevertheless, a slight increase in the n-alkane chain length from C 10 H 22 to C 12 H 26 greatly enhances the capability of nalkane in suppressing the diffusional degradation of miniemulsion droplets. [12], ( ) Baker [17], ( ) Franks [18], (+) McAuliffe [19], ( ) Sutton and Calder [20], ( ) Taylor [21], () Kabalnov et al [22], (R) Tolls et al [23], (×) Eastcott et al [24].…”

Solubility and Dissolution of Drug Product: A Review

“…the higher its molecular weight) the less soluble the substance will be. For example, within alkanes, molecular size is the primary determinant of their solubility in water, and increasing molecular size results in a decrease in water solubility mainly due to the increased free energy penalty for cavity formation in water 5 .…”

Influence of sulfur oxidation state and steric bulk upon trifluoromethyl ketone (TFK) binding kinetics to carboxylesterases and fatty acid amide hydrolase (FAAH)

“…The alkane chains were built in the fully extended alltrans conformation, consistent with recent experimental data for aqueous-phase saturated alkanes. 56 All structures were optimized using Density Function Theory with the Becke 3-parameter hybrid exchange functional 57 and Lee-Yang-Parr gradient corrected electron correlation functional 58 (B3LYP) using a double zeta correlation consistent basis set with diffuse basis functions (aug-cc-pVDZ) (for overview of basis sets see Cramer 59 ). All quantum chemical calculations were performed using Gaussian 03 Rev.…”